No quick fix for strokes, but L.A. trial made care speedier, better

Perry C. Riddle

Dr. Sidney Starkman, coauthor of a clinical trial that tested a stroke treatment across Los Angeles, awaits a stroke victim at the UCLA Medical Center. The trial dramatically changed stroke care in the Southland.

A groundbreaking Los Angeles clinical trial has proven a disappointment in demonstrating that a safe and inexpensive mineral infusion could reduce disability in stroke patients. But the researchers behind a UCLA trial called "Fast-Mag" said the eight-year effort drove dramatic improvements in the care of stroke victims across the Southland, rallying hospitals, emergency medical teams and physicians to deliver faster and more targeted care.

Among 1,700 Los Angeles-area subjects who suffered a stroke between 2005 and 2012, UCLA neurologist Dr. Jeffrey Saver reported Thursday, those who got magnesium sulfate infusions for two days fared no better three months later than those who got a placebo infusion. For now, at least, the trial's outcome appears to dash hopes that magnesium sulfate, a cheap and long-used treatment for the pregnancy complication preeclampsia, would help protect brain cells from injury when their blood supply is compromised.

But the trial's innovative procedures appear to have radically changed the speed with which the care of patients with stroke symptoms starts. In a medical specialty whose mantra is "time is brain," that extra speed promises to pay rich dividends in saving more brain cells, and improving patients' ability to emerge intact after a stroke.

At the outset of the trial, an estimated 2 to 3% stroke patients were coming into the care of hospital specialists within three hours. That's important because three hours from the onset of stroke symptoms is the timeframe in which a clot-busting medication called tissue plasminogen activator (tPA) is likely to help.

In the Fast-Mag trial, nearly three-quarters of subjects were en route to stroke centers and already undergoing treatment in the hands of first responders within an hour of the onset of symptoms, said Saver, speaking Thursday to the American Stroke Assn.'s international conference in San Diego.

"These are previously unachieved timeframes in stroke," Saver told The Times on Thursday. "It really has opened up a new time window for promising future therapies."

In 2005, when UCLA researchers enrolled their first subjects in a trial to test the benefits of magnesium sulfate for stroke, getting patients with stroke symptoms into care quickly was almost incidental. Researchers believed that initiating the magnesium sulfate infusion within two hours of the onset of symptoms would be crucial.

So the study's authors devised a new screening test to identify stroke. They revamped procedures to speed the ambulance delivery of potential stroke patients, and streamlined the intake process at hospitals receiving them. They trained 3,000 paramedics from 40 different emergency agencies across Southern California to broker a complex informed consent process, administer the stroke screen, and begin the infusion.

And eventually, they devised a system of some 30 elite stroke centers across Southern California, and rerouted patients with stroke symptoms to units best equipped to treat them.

"It was a herculean effort," said USC emergency physician Marc Eckstein, medical director of the Los Angeles Fire Dept. and a study coauthor. At all levels, he said, "it really created a new level of urgency" in caring for these patients.

Ironically, getting patients into better care faster may have overshadowed any effects that a rapid infusion of magnesium sulfate might have had, said Dr. Saver. Both subjects getting placebos and those getting the Fast-Mag treatment were sped into optimal care, he noted. Three months after their stroke, that improved response likely benefited both equally.

"That's distressing for trial designers. But it's good for patients," said Saver, who said he would be content with that outcome.

The Fast-Mag study has not only made Los Angeles a model for other major metropolitan cities: it has established the infrastructure to make Los Angeles a testbed for future therapies that require emergency medical response that must be extra fast and closely coordinated across jurisdictional lines.

The team of Fast-Mag investigators has joined a national consortium of research centers established by the National Institutes of Health to conduct large-scale trials of emergency interventions to reduce the damage done by stroke, seizures, spinal cord and traumatic brain injury.

"It's a model for future work," said coauthor Sidney Starkman, a UCLA neurologist.